Category Archives: WHO Classification

Organ Systems, Lymph Node, WHO Classification

EBV+ T-Cell Lymphoproliferative Disorders of Childhood

This is a rare disorder of clonal EBV-infected T-cells, which contain an activated cytotoxic phenotype.  There is some clinicopathologic overlap with aggressive NK-cell leukemia.  May be associated with acute or chronic EBV infection.
Immunophenotypic Expression Pattern
Marker
Comment
Positive
Positive
Negative
TIA-1
Positive
Positivity is associated with chronic active EBV infection.
Positivity is associated with acute primary EBV infection.
EBV (EBER)
Positive
References
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Bone Marrow, WHO Classification

Aggressive NK-Cell Leukemia

This is an “aggressive” leukemia/lymphoma disorder, which is almost always associated with EBV.  Location of involvement can range from peripheral blood to bone marrow, spleen, and, liver.  Any organ can be involved.
Immunophenotypic Expression Pattern
Marker
Comment
Positive
Surface negative.  Cytoplasmic CD3ε positive.
Positive
TIA-1
Positive
Positive
References
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Lymph Node, Gastrointestinal, WHO Classification

Enteropathy-Associated T-cell Lymphoma

Immunophenotypic Expression Pattern
Marker
Comment
Positive
Positive
Negative
Negative
Positive
Negative (+ in a subset)
Negative
EBV (EBER)
Negative
Positive
Perforin
Positive
TIA-1
Positive
Variable.  Usually has at least some subset expression (varying intensity).
Negative
Negative
Negative
References
Parker, A., et. al.  “Best Practice in Lymphoma Diagnosis and Reporting.”  British Committee for Standards in Haematology, Royal College of Pathologists.  April, 2010.
 
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.  pp. 289-91.
Organ Systems, Lymph Node, WHO Classification

Extranodal NK/T Cell Lymphoma, Nasal Type

Immunophenotypic Expression Profile
Marker
Comment
Positive
Usually Negative (Surface negative, cytoplasmic epsilon positive)
CD3-ε
Positive (cytoplasmic)
Negative
Negative
Positive
Negative (a few cases are positive)
Positive
Positive
Positive. Not specific for extra nodal NK/T-cell lymphoma, and may be expressed in other T-cell lymphomas.
EBV (EBER)
Positive.  Negative cases should be re-evaluated very closely.
Positive
Perforin
Positive
TIA-1
Positive
Negative
Negative
Negative
References
Parker, A., et. al.  “Best Practice in Lymphoma Diagnosis and Reporting.”  British Committee for Standards in Haematology, Royal College of Pathologists.  April, 2010.
 
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.  pp. 287-88.
Organ Systems, Bone Marrow, WHO Classification

T-Cell Prolymphocytic Leukemia (T-PLL)

T-PLL is an aggressive T-cell leukemia composed of small to medium-sized post-thymic T-cells, which usually have a nucleolus (Up to 25% of cases may not have visible nucleoli).  Most patients will have generalized lymphadenopathy in addition to hepatosplenomegaly.  Up to 20% of cases will have skin involvement.
Charateristic Immunophenotypic Profile
 
Stain
Comment
Negative
Negative
Positive
Positive
Positive
CD4+/CD8-
CD4+/CD8+
CD4-/CD8+
~60% of cases
~25% of cases
~15% of cases
TCL1
Positive
References
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Bone Marrow, WHO Classification

T-cell Large Granular Lymphocytic Leukemia (T-LGL)

T-LGL leukemia represents only 2-3% of mature lymphocytic leukemias.  Classically patients present with neutropenia and splenomegaly.  Most patients don’t die from the leukemia itself, but accompanying diseases/cytopenias.  The peripheral blood LGL count is usually between 2-20x10e9/L.  THere is a significant gray-zone of uncertainty between what constitutes a benign population of LGLs and a neoplastic process (possibly an immune response that turns neoplastic??).
Features
  • Pathophysiology is NOT well understood
  • STAT3 mutated in approximately 1/3rd of cases (rarely STAT5B)
  • LGL count >2,000/μL (cases with <2,000/μL can be diagnosed if all other criteria are consistent with T-LGL leukemia
    • “All other criteria” are not well-described
  • Cases that resemble T-LGL but lack surface CD3 (sCD3) are classified in the NK-cell disorders.
Characteristic Immunophenotype
Stain
Comment
Positive
Usually Negative.  A subset of cases may express CD4.  CD4 + cases have been associated with an underlying malignancy  (~30% of cases).
+/- (May have diminished or lost expression)
+/- (May have diminished or lost expression)
Usually Positive
Granzyme_B
Usually Positive
TIA-1
Positive
CD57
Positive (>80% of cases)
Usually negative
References
Swerdlow SH, Campo E, Harris, NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds):  WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017
 
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Bone Marrow, Lymph Node, WHO Classification

B-ALL

B-Cell Acute Lymphoblastic Leukemia/Lymphoma (B-ALL) accounts for ~80-85% of ALL cases.  75% occur in children < 6 years of age.  The remainder of ALL cases are of T-cell origin.  T-ALL more commonly presents as extra nodal disease.
Immunohistochemical Profile
Stain
Comment
Positive
Positive.  Up to 10% of T-ALL cases may be positive.
Positive in most cases.  CD10 negative cases may be associated with MLL gene rearrangements.
Variably positive.
CD22
Positive (cytoplasmic)
Variably positive.  t(12;21) and hyperploidy cases are often CD34+.
+/-
Positive.  Approximately 95% sensitive.
CD13
+/-  Myeloid markers do not exclude the possibility of an ALL.
+/-  Myeloid markers do not exclude the possibility of an ALL.
MPO
Negative.  Positivity would support either an AML or a B/myeloid leukemia.
Typically Negative
Expression is associated with t(9;22) in adults.
Positive (nuclear expression).  Sensitive and specific marker of B-cell lineage, but a subset of AMLs may express PAX-5 [t(8;21)].
MPO – myeloperoxidase
References
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Lymph Node, WHO Classification

Burkitt Lymphoma

Burkitt lymphoma is a high grade B cell lymphoma composed of medium-sized monomorphic lymphoid cells. The cytology of the nuclei includes finely dispersed chromatin. By touch prep, the cells resemble lymphoblasts, often with cytoplasmic lipid filled vacuoles. In tissue section, the nuclear appearance can be variable from regular round appearance to that with more irregularity. Continue reading Burkitt Lymphoma →